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| Name | Class |
|---|---|
| Stin Pharma | UNKNOWN |
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Rehabilitation of knee stability and function after anterior cruciate ligament (ACL) reconstruction is slow and costly. The use of anabolic steroids, such as oxandrolone, may aid in the recovery of muscle mass and strength, as well as functional capacity. Oxandrolone, derived from dihydrotestosterone, has high anabolic activity and low androgenic activity (a 13:1 ratio), making it more effective in promoting weight gain with fewer side effects compared to other steroids. Registered by the FDA and previously by ANVISA (National Health Surveillance Agency (Brazil), it is indicated for cases of post-trauma or post-surgery weight loss. The subdermal use of oxandrolone implants is proposed to release the drug directly into the bloodstream, improving efficacy and reducing issues related to oral administration. This study evaluates the safety and tolerability of the absorbable subdermal oxandrolone implant for 24 weeks versus placebo implant in both men and women as an adjuvant treatment during rehabilitation following anterior cruciate ligament (ACL) surgical reconstruction. The serum and pharmacokinetic profile of the oxandrolone implant will be monitored.
This is a phase II, randomized, double-blind, placebo-controlled, multicenter clinical study designed to evaluate the safety and tolerability profile of the absorbable oxandrolone implant as an adjuvant treatment in rehabilitation following anterior cruciate ligament (ACL) reconstruction surgery. The primary safety outcome will be the incidence of serious adverse events (SAEs) related do treatment collected through spontaneous reports and/or clinical findings over 24 weeks after randomization (subdermal insertion of the absorbable oxandrolone implant). The effectiveness of absorbable oxandrolone implants in the rehabilitation of patients after surgical ACL reconstruction will be evaluated in an exploratory manner, based on their effects on the recovery of muscle mass, muscle strength, and functional capacity.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Oxandrolone | Experimental | Absorbable oxandrolone implant (subdermal insertion) Men: 400 mg oxandrolone (two 200 mg oxandrolone implants each) Women: 200 mg oxandrolone (one 200 mg oxandrolone implant) |
|
| Placebo | Placebo Comparator | Absorbable placebo implant (excipients; subdermal insertion) Men: 400 mg placebo (two 200 mg placebo implants each) Women: 200 mg placebo (one 200 mg placebo implant) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oxandrolone | Drug | Absorbable oxandrolone implant (subdermal insertion) Men: 400 mg oxandrolone (two 200 mg oxandrolone implants each) Women: 200 mg oxandrolone (one 200 mg oxandrolone implant) |
| Measure | Description | Time Frame |
|---|---|---|
| Combination of serious adverse events (SAEs) related to treatment accumulated within 24 weeks of oxandrolone or placebo pellet insertion and collected through spontaneous reporting and/or clinical findings | The primary safety outcome is a composite of serious adverse events (SAEs) related to treatment accumulated over 24 weeks following oxandrolone or placebo implant insertion, collected from the time of informed consent signature through spontaneous reports and clinical findings. | From randomization to the end of study on Week 24. |
| Measure | Description | Time Frame |
|---|---|---|
| Participants who experience androgenization | The appearance and worsening of signs of androgenization in female participants will be monitored at all clinical visits throughout the study. A physician or other qualified professional will assess hirsutism, alopecia, and acne, and the assessment of voice deepening will be performed by the participant´s self-report. | At pre-insertion and 4, 12 and 24 weeks after randomization |
| Measure | Description | Time Frame |
|---|---|---|
| Anthropometric Measurement Assessment | Measurements of weight, height, waist circumference, and hip circumference should be collected to calculate anthropometric indices related to cardiovascular risk in the development of diseases and comorbidities: Body Mass Index (BMI), Body Adiposity Index (BAI), Waist-to-Hip Ratio (WHR), and Waist-to-Height Ratio (WHR). The parameters will be collected during the physical examination at all in-person visits. |
Inclusion Criteria:
For male and female participants:
For male participants only:
- Total PSA ≤ 4.1 ng/mL.
Exclusion criteria:
For female participants only:
For male participants only:
- Known or suspected carcinoma of the prostate or male breast;
For male and female participants:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Leandro B Agati, PhD | Contact | +55 11 4040-8670 | agati@svriglobal.com | |
| Viviane Santana | Contact | +55 11 4040-8670 | viviane.santana@svriglobal.com |
| Name | Affiliation | Role |
|---|---|---|
| Roberto Tauchmann, MD | Hospital do Rocio | Principal Investigator |
| André Malavasi, MD, PhD | Science Valley | Study Chair |
| Eduardo Ramacciotti, MD, PhD |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Unimed Fortaleza | Recruiting | Fortaleza | Ceará | Brazil |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34982051 | Background | Weber AE, Gallo MC, Bolia IK, Cleary EJ, Schroeder TE, Rick Hatch GF 3rd. Anabolic Androgenic Steroids in Orthopaedic Surgery: Current Concepts and Clinical Applications. J Am Acad Orthop Surg Glob Res Rev. 2022 Jan 4;6(1):e21.00156. doi: 10.5435/JAAOSGlobal-D-21-00156. | |
| 15025546 | Background | Orr R, Fiatarone Singh M. The anabolic androgenic steroid oxandrolone in the treatment of wasting and catabolic disorders: review of efficacy and safety. Drugs. 2004;64(7):725-50. doi: 10.2165/00003495-200464070-00004. |
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| Placebo | Drug | Absorbable placebo implant (excipients; subdermal insertion) Men: 400 mg placebo (two 200 mg placebo implants each) Women: 200 mg placebo (one 200 mg placebo implant) |
|
| Biochemical profile | Composite of the number of participants who experience laboratory values for biochemical, metabolic, hormonal, and haemostasis profile outside the reference range and/or deemed clinically significant over the 24 weeks following randomisation. The following blood tests will be performed: Biochemical profile: haematocrit, platelet count, creatinine, serum urea, total bilirubin, aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), creatine phosphokinase (CPK), total prostate-specific antigen (PSA). | At pre-insertion, 4, 12, and 24 weeks after randomization |
| Metabolic Profile | Composite of the number of participants who experience laboratory values for biochemical, metabolic, hormonal, and haemostasis profile outside the reference range and/or deemed clinically significant over the 24 weeks following randomisation. The following blood tests will be performed: Metabolic profile - total cholesterol, LDL, HDL, lipoprotein A. | At pre-insertion, 4, 12, and 24 weeks after randomization |
| Hormonal Profile | Composite of the number of participants who experience laboratory values for biochemical, metabolic, hormonal, and haemostasis profile outside the reference range and/or deemed clinically significant over the 24 weeks following randomisation. The following blood tests will be performed: Hormonal profile: serum concentration of total testosterone, free testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). | At pre-insertion, 4, 12, and 24 weeks after randomization |
| Hemostasis Parameters | Composite of the number of participants who experience laboratory values for biochemical, metabolic, hormonal, and haemostasis profile outside the reference range and/or deemed clinically significant over the 24 weeks following randomisation.The following blood tests will be performed: Haemostasis parameters - D-dimer, SHBG, and free S-protein. | At pre-insertion, 4, 12, and 24 weeks after randomization |
| Total serum oxandrolone concentration | In a subgroup of 20 participantes from selected centres, serum oxandrolone concentrations will be assessed to determine the oxandrolone concentration. Serum samples will be processed and stored for analysis by Liquid Chromatography coupled to Tandem Mass Spectrometry (LC-MS/MS) in a central laboratory. | Pre-insertion of the oxandrolone implant; various times after the insertion of the oxandrolone implant and 24 hours; 1, 2, 3, 4, 8, 12, 16, 20, and 24 weeks. |
| Area under the curve (AUC) | The pharmacokinetic profile of oxandrolone will be characterised in a subgroup of participants (N = 20) by Liquid Chromatography coupled to Tandem Mass Spectrometry (LC-MS/MS) | Pre-insertion of the oxandrolone implant and various times after the insertion of the oxandrolone implant: 24 hours; 1, 2, 3, 4, 8, 12, 16, 20, and 24 weeks. |
| Maximum concentration (Cmax) | The pharmacokinetic profile of oxandrolone will be characterised in a subgroup of participants (N = 20) by Liquid Chromatography coupled to Tandem Mass Spectrometry (LC-MS/MS) | Pre-insertion of the oxandrolone implant and various times after the insertion of the oxandrolone implant: 24 hours; 1, 2, 3, 4, 8, 12, 16, 20, and 24 weeks. |
| Time to reach maximum concentration (tmax) | The pharmacokinetic profile of oxandrolone will be characterised in a subgroup of participants (N = 20) by Liquid Chromatography coupled to Tandem Mass Spectrometry (LC-MS/MS) | Pre-insertion of the oxandrolone implant and various times after the insertion of the oxandrolone implant: 24 hours; 1, 2, 3, 4, 8, 12, 16, 20, and 24 weeks. |
| Half Life (t1/2) | The pharmacokinetic profile of oxandrolone will be characterised in a subgroup of participants (N = 20) by Liquid Chromatography coupled to Tandem Mass Spectrometry (LC-MS/MS) | Pre-insertion of the oxandrolone implant and various times after the insertion of the oxandrolone implant: 24 hours; 1, 2, 3, 4, 8, 12, 16, 20, and 24 weeks. |
| At pre-insertion and 4, 12 and 24 weeks after randomization |
| Changes in the Short Form Health Survey SF-36 Quality of Life Questionnaire | Number of participants with changes in the 36-Item Short Form Health Survey (SF-36). SF-36 is a patient-reported outcome (PRO) measure evaluating a participant's health status. It comprises 36 items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. Items from 8 domains contribute to the PCS. The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health | At pre-insertion, 12 and 24 weeks after randomization |
| Changes in the General Anxiety Disorder Questionnaire (GAD-7) | The GAD-7 is a self-administered questionnaire that assesses generalized anxiety, composed of seven questions covering aspects such as excessive worry, difficulty controlling worry, irritability, muscle tension, fatigue, difficulty relaxing, and sleep problems. Each question is scored from 0 to 3, with a severity score ranging from 0 to 21. Cutoff points are ≥5 for mild anxiety, ≥10 for moderate anxiety, and ≥15 for severe anxiety. | At pre-insertion, 12 and 24 weeks after randomization |
| Changes in the Patient Health Questionnaire (PHQ-9) | The PHQ-9 is a self-administered questionnaire focused on depression, consisting of nine questions addressing aspects like diminished interest, depressed mood, fatigue, sleep issues, appetite changes, low self-esteem, difficulty concentrating, slowed movements or agitation, and suicidal thoughts. Each question is scored from 0 to 3, with a severity score from 0 to 27. Severe depression is indicated by a score >16. | At pre-insertion, 12 and 24 weeks after randomization |
| Changes in the Patient Acceptable Symptom State (PAS) | The PAS is a method used to assess whether the current symptom state of a patient is acceptable to them, considering their personal perspective of well-being and functionality. It consists of a single standardized question that captures the patient's global satisfaction with their current condition. | At pre-insertion, 12 and 24 weeks after randomization |
| Changes in the Lysholm Knee Scoring Scale | The Lysholm Knee Scoring Scale provides a quantification of knee function, allowing comparison of a patient's progress over time. It consists of 8 items. These items are divided into two categories: (1) Symptoms, which evaluate pain, locking, and instability; and (2) Function, which assesses the ability to climb stairs, run, perform daily activities, and squat. The participant responds to each item, which is scored according to the severity or frequency of the symptoms. The total score ranges from 0 to 100 points, with 100 representing the best possible outcome (indicating ideal knee function) and 0 representing the worst outcome (indicating severe dysfunction or disability of the knee). | At pre-insertion, 12 and 24 weeks after randomization |
| Satisfaction with Treatment | Participants will be asked to rate their satisfaction by choosing one of the following options (ranging from 1 to 5): very satisfied, satisfied, not sure, dissatisfied, or very dissatisfied. | At 24 weeks after randomization |
| Changes in the Y Balance Test | Changes in the Y Balance Test will be conducted in a subgroup of participants at selected research centres with appropriate infrastructure available (N = 40). The Y Balance Test is a functional assessment used to measure mobility, muscle strength, and trunk and lower limb stability. It is used to identify muscle imbalances, strength deficiencies, and injury risks in individuals recovering from injuries. The final test score is the distance reached in each direction, expressed as a percentage of leg length (adjusting the results based on body size). Comparisons are made between limbs (right leg vs. left leg) to check for symmetry and identify possible deficiencies or imbalances. The patient must achieve less than 4cm of anterior reach difference between legs. | At pre-insertion,12 and 24 weeks after randomization |
| Changes in body composition | Changes in body composition will be conducted in a subgroup of participants at selected research centres with appropriate infrastructure available (N = 40). Bioimpedance is a non-invasive procedure that measures a person's body composition. Four electrodes are applied to the participant's hands and feet. The equipment emits a mild electrical current that passes between the individual's body tissues. The device detects the voltage drop caused by impedance and identifies the body's resistance and reactance. In this way, the participant's lean mass (Kg) and fat mass (%) are obtained. | At pre-insertion and 12 and 24 weeks after randomization |
| Thigh Volume by Magnetic Resonance Imaging. | Thigh Volume by Magnetic Resonance Imaging will be conducted in a subgroup of participants at selected research centres with appropriate infrastructure available (N = 40). Hydrogen magnetic resonance imaging (¹H-MRI) will be performed using a 1.5 Tesla scanner with the body coil functioning as both transmitter and receiver, as available at the research centre. Nine axial images of the thigh will be acquired after obtaining a coronal image of scouting weighted by longitudinal relaxation time (repetition time/echo time weighted by longitudinal relaxation time of 300/echo time), which will be used to identify the exact anatomical location for the axial images. | At pre-insertion and 12 weeks after randomization |
| Changes in maximal muscle strength using isometric dynamometry | Changes in maximal muscle strength will be conducted in a subgroup of participants at selected research centres with appropriate infrastructure available (N = 40).The Isometric dynamometry evaluates isometric strength using the Lafayette Isometric Hand Dynamometer or its national equivalent. The evaluation will be performed by a physiotherapist on the study team for the knee extensors and flexors. The parameters used in the assessment are defined by the literature: normalisation and symmetry index; peak torque (Nm) of the quadriceps; limb symmetry index (LSI). | At pre-insertion, 12 and 24 weeks after randomization |
| Science Valley |
| Study Director |
| Faculdade Ciências Médicas de Minas Gerais (CMMG) | Recruiting | Belo Horizonte | Minas Gerais | Brazil |
|
| Centro de Oncologia do Paraná | Recruiting | Curitiba | Paraná | Brazil |
|
| Unimed Brusque | Recruiting | Brusque | Santa Catarina | Brazil |
|
| Hospital e Maternidade Christóvão da Gama | Recruiting | Santo André | São Paulo | Brazil |
|
| Santa Casa de Santos | Recruiting | Santos | São Paulo | Brazil |
|
| 25683732 | Background | Thomas AC, Wojtys EM, Brandon C, Palmieri-Smith RM. Muscle atrophy contributes to quadriceps weakness after anterior cruciate ligament reconstruction. J Sci Med Sport. 2016 Jan;19(1):7-11. doi: 10.1016/j.jsams.2014.12.009. Epub 2015 Jan 13. |
| 23689765 | Background | Bauman WA, Spungen AM, Collins JF, Raisch DW, Ho C, Deitrick GA, Nemchausky BA, Goetz LL, Park JS, Schwartz M, Merritt JL, Jayawardena V, Sandford P, Sabharwal S, Holmes SA, Nasar F, Sasaki R, Punj V, Zachow KF, Chua WC, Thomas MD, Trincher RC. The effect of oxandrolone on the healing of chronic pressure ulcers in persons with spinal cord injury: a randomized trial. Ann Intern Med. 2013 May 21;158(10):718-26. doi: 10.7326/0003-4819-158-10-201305210-00006. |
| 28840147 | Background | Wu B, Lorezanza D, Badash I, Berger M, Lane C, Sum JC, Hatch GF 3rd, Schroeder ET. Perioperative Testosterone Supplementation Increases Lean Mass in Healthy Men Undergoing Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Trial. Orthop J Sports Med. 2017 Aug 9;5(8):2325967117722794. doi: 10.1177/2325967117722794. eCollection 2017 Aug. |
| ID | Term |
|---|---|
| D055948 | Sarcopenia |
| ID | Term |
|---|---|
| D009133 | Muscular Atrophy |
| D020879 | Neuromuscular Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D001284 | Atrophy |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| D010074 | Oxandrolone |
| ID | Term |
|---|---|
| D000732 | Androstanols |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
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